Sulfuric acid magnesium salt (1:1) → 2-[1-(Tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinolin-4-ylamino]thiazole-4-carboxylic acid ethyl ester

HRID 14650

Reaction equation

[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[CH:16][C:17]=2[O:19][CH3:20])[C:12]([NH:23][C:24]([NH2:26])=[S:25])=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:29][C:30](=O)[C:31]([O:33][CH2:34][CH3:35])=[O:32].[O-]S([O-])(=O)=O.[Mg+2]>CC(C)=O>[CH2:34]([O:33][C:31]([C:30]1[N:26]=[C:24]([NH:23][C:12]2[C:13]3[C:18](=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=3)[C:9]([CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:27])=[N:10][CH:11]=2)[S:25][CH:29]=1)=[O:32])[CH3:35]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (6,8-dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester (62 mg, 0.158 mmol) and ethyl bromopyruvate (37.7 mg, 0.174 mmol) in acetone (1.6 mL) was added MgSO4 (9.5 mg, 0.079 mmol). The resulting suspension was stirred at 60° C. for 3 h. The reaction was cooled to RT and concentrated. The residue was purified by passing through a 5 g silica cartridge eluting with 2% MeOH in DCM to give 2-[1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinolin-4-ylamino]thiazole-4-carboxylic acid ethyl ester as a pale yellow solid (32.5 mg, 42%). 1H-NMR (CDCl3): δ, 8.53 (s, 1H), 7.47 (s, 1H), 6.82 (s, 1H), 6.61 (s, 1H), 5.07 (d, 2H, J=4.2 Hz), 4.41 (q, 2H, J=7.2 Hz), 4.00 (s, 3H), 3.89 (s, 3H), 1.52 (s, 9H), 1.41 (t, 3H, J=7.3 Hz); MS: calculated for C23H28N4O6S+H 489.0; found: 489.0.

Workup

temperatureThe reaction was cooled to RT
concentrationconcentrated
customThe residue was purified
washeluting with 2% MeOH in DCM

Sources & evidence

ORD record: ord-9e7236acfd6e427693c7df328b1f75c4
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07732446B1

Linked notes

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